title: Harmful effect of ERβ on BCRP-mediated drug resistance and cell proliferation in ERα/PR-negative breast cancer.
abstract: The role of estrogen receptor β (ERβ) in breast cancer is still under investigation. Various studies have provided evidence that ERβ behaves as a tumor suppressor in breast cancer, whereas some studies of estrogen receptor α (ERα) negative breast cancer reported a positive correlation between high ERβ expression and poor prognostic phenotypes, such as induced proliferation, invasion and metastasis. In the present immunohistochemistry study of 99 ERα/progesterone receptor (PR)-negative breast cancer samples, nuclear expression of ERβ was positively associated with membranous expression of breast cancer resistance protein (BCRP), Ki67 (proliferation marker) and tumor size. Moreover, both endogenous and exogenous ERβ upregulated BCRP expression which induced BCRP-mediated drug resistance and enhanced proliferation of ERα-/PR- breast cancer cells in the presence of 17β-estradiol, whereas these effects were reversed by additional use of tamoxifen (TAM). In addition, the regulation of BCRP via specific binding between ERβ and estrogen response element (ERE) was demonstrated in an electrophoretic mobility shift assay. Overall, our findings manifest that ERβ might act as a tumor promoter of cell proliferation and BCRP-mediated drug resistance in ERα-/PR- breast cancer. TAM routinely used for patients with ERα+/PR+, ERα+/PR- and ERα-/PR+ breast cancer might also be effective in ERα-/PR- but ERβ+ breast cancer. Therefore, the detection of ERβ in clinic is valuable and should not be neglected in breast cancer, especially for the ERα-/PR- phenotype.
authors.affiliation: Department of Pathology and Pathophysiology, Shandong University School of Medicine, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Jia
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Qin
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhang
authors.forename: Gengyin
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D024202:Electrophoretic Mobility Shift Assay; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D018931:Antineoplastic Agents, Hormonal; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D013629:Tamoxifen; C116614:ABCG2 protein, human; C506487:ESR1 protein, human; C508053:ERBB2 protein, human
keywords: BCRP; E2; ERE; ERα/PR-negative breast cancer; ERβ; TAM; cell proliferation